Strategies to Improve Influenza Vaccine Efficacy in High-Risk Obese Individuals

项目摘要 疫苗接种对于控制每年的流感流行和大流行至关重要，但疫苗的有效性较低 在高风险人群中，如肥胖症患者。2009年H1N1流感大流行后，肥胖被确定为 是增加流感疾病严重程度的独立高危因素。我们实验室的研究表明， 宿主不仅比非肥胖宿主更易患严重流感疾病， 通过佐剂疫苗接种。这些令人不安的差异突出了发展流感的迫切需要 随着全球肥胖率稳步上升，疫苗可以更好地保护这一高危人群。我们的实验室正在使用 建立了遗传或饮食诱导的肥胖小鼠模型，通过研究 提高疫苗在肥胖宿主中效力的策略。我们有初步数据显示我们可以拯救 通过4周前引入减肥干预，降低了我们肥胖小鼠的疫苗效力 预防针该提案将1）定义疫苗有效性所需的减肥“窗口”，2）评估 与疫苗效力相关的体液反应的变化。该提案将评估各种机制， 在疫苗接种前体重减轻相关的疫苗效力增加的背后。如果这些机制 可以阐明，佐剂可以被设计为靶向相同的途径，以克服与免疫相关的问题。 标准护理疫苗。这项研究的结果将有实质性的翻译影响， 提高疫苗对其他传染病的效力，以更好地保护我们的高危人群， 公共卫生

PROJECT SUMMARY Vaccination is critical for controlling annual influenza epidemics and pandemics, but vaccines are less effective in high-risk populations such as people with obesity. After the 2009 H1N1 pandemic, obesity was identified as an independent high-risk factor for increased influenza disease severity. Work by our lab has shown that obese hosts are not only more susceptible than non-obese hosts to severe influenza disease but also less protected by adjuvanted vaccination. These disconcerting differences highlight the immediate need to develop influenza vaccines that better protect this high-risk group as global obesity rates rise steadily. Our laboratory is using established mouse models of obesity, induced either genetically or by diet, to address this need by investigating strategies to improve vaccine efficacy in obese hosts. We have preliminary data showing that we can rescue the decreased vaccine efficacy in our obese mice by introducing a weight loss intervention 4-weeks before vaccination. This proposal will 1) define the weight-loss “window” required for vaccine efficacy and 2) assess the changes in humoral responses that correlate with vaccine efficacy. This proposal will evaluate the mechanisms behind the increased vaccine efficacy associated with weight loss before immunization. If these mechanisms can be elucidated, adjuvants can be designed to target the same pathways to overcome the problems with the standard of care vaccines. The results of this research will have substantial translational implications for improving vaccine efficacy for other infectious diseases to protect our high-risk populations better and improve public health.